_slides_pmi285-wu-2-jan_04

_slides_pmi285-wu-2-jan_04 - Oxidative Stress oxidants...

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Oxidative Stress oxidants antioxidants Reactive oxygen species Reactive nitrogen species Free radicals Vitamin C, E Carotenoids, Se Glutathione, Thioredoxin Specific enzymes: SOD, Catalase
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Oxidative Stress • What are oxygen radicals or reactive oxygen species? • How reactive are reactive oxygen species? • How are reactive oxygen species generated in the cell? • How do cells protect themselves against reactive oxygen species ?
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Oxygen Radicals and Reactive Oxygen Species •O 2 , O 3 • Superoxide anion, O 2 - . • Hydrogen peroxide • Hydroxyl Radical • Hypochlorous acid, HOCl • Aldehyde • NO, NO 2 , Peroxynitrite • Lipid alkoxyl radicals • Lipid peroxyl radicals
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Reactive Oxygen Species Half-life O 2 O 3 H 2 O 2 O 2 -. . OH RO . ROO . NO . ONOO - oxygen (in water) ozone hydrogen peroxide superoxide anion hydroxy radical alkoxyl radical peroxyl radical nitric oxide peroxynitrite 10 -6 sec stable (not occur in vivo) stable spontaneous dismutation 10 -9 sec 10 -6 sec 7 sec 5.6 sec (0.1 sec in heart) 1-2 sec
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Free Radicals: Definition A free radical is defined as any species that contains one or more unpaired electron occupying an atomic or molecular orbital by itself . e.g. O 2 Box diagram Lewis dot diagram
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Free Radical: Chain Reaction Unpaired electron can serve as an electron donor (nucleophilic)or as a receiver. + R C (R-C) R +C R+ C R-C + C R (electrophilic) + R R C (nucleophilic) + C (Note: Transition metals, such as Fe and Cu, can also serve as an electron donor or as a receiver)
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Lipid Peroxidation •Any free radical generated close to membrane can attack the unsaturated fatty acid side chains of the phospholipid of membrane. •Transition metal will accelerate this reaction. R--C -H + HO R--C + H 2 O carbon-centered radical R--C - OO peroxyl radical R--C + O 2 R--C -OO + R’-H R--C- OOH + R’ lipid hydroperoxide R--CHO (e.g. malondialdehyde, 4-hydroxynonenal) R--C-OOH CH 3 (CH 2 )--CH--C = C -CHO + Protein-SH OH H CH 3 (CH 2 )--CH--CH - CH 2 -CHOH O H 4-hydroxynonenal S-protein protein CH NH - CH N = CH protein-NHCH=CH-CH=N-protein (Intermolecular cross-link) CHO--CH 2 --CHO + NH 2 --protein--NH 2 (Intramolecular cross-link) Malondualdehyde + 2 Protein-SH
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Transition Metal Ion in Lipid Peroxidation R - OOH + Fe +2 R - O + Fe +3 + OH - alkoxyl radical R - OOH + Fe +3 R - OO + Fe +2 + H + peroxyl radical R - O + R’-H R - OH + R’ R - OO + R”-H R -OOH + R” R’ + O 2 R’ -OO
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Prooxidant Effect •Most antioxidants are capable to generate oxidants through the chemical nature of their redox cycle. •Free radical molecule can be generated from antioxidant through the catalysis of a transition metal. O - C = C -OH + Fe +2 + H + HO -C = C -OH + Fe +3 Normally: 2 O - C = C - OH + 2H+ O = C - C = O + HO - C = C - OH When oxygenation: 2 O - C = C - OH + O 2 O = C - C = O + H 2 O 2 (dehydro- )
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One-electron Reduction Potential 2.4 1.6 0.8 0.0 Reduction Potential (E 0 /Volts) HO , H + /H 2 O RO , H + /ROH ONOOH/ NO 2 ROO , H + /ROOH NO 2 /NO 2 - GS /GS - Ascorbate - , H + /ascorbate monoanion Fe +3 -EDTA/Fe +2 -EDTA
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Formation of Oxidants Electron-Transfer Reactions O 2 e - e - e - e - O 2 - HO H 2 O H 2 O 2 0 H Hydroxyl radical Superoxide anion
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This note was uploaded on 12/30/2010 for the course PMI 285 taught by Professor Wu during the Winter '04 term at UC Davis.

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_slides_pmi285-wu-2-jan_04 - Oxidative Stress oxidants...

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